Implementing the continual reassessment method (CRM)

One of the aims of a phase I trial in oncology is to find the maximum tolerated dose. A set of doses is administered to participants starting from the lowest dose in increasing steps. To do this safely, the toxicity of each dose is assessed, and a decision is made about whether to proceed with the next highest dose until the desired target toxicity level is found. A suitable dose is then chosen to take forward into phase II studies to discover whether this drug is efficacious. The majority of oncology phase I trials use algorithm-based rules such as the 3 + 3 design to escalate doses; the 3 + 3 design is easy to implement by nonstatisticians but is statistically inefficient. Other designs, such as the continual reassessment method (O'Quigley, Pepe, and Fisher 1990), use a model to help guide the decision of which dose to give. The complexity of the CRM and that it requires software may be reasons why it is not more widely used. This talk will describe a new command crm that is a Mata implementation of the CRM and includes some discussion about the programming difficulties.